Transient Prehypertensive Treatment In Spontaneously Hypertensive Rat: A Comparison Of Losartan And Amlodipine Regarding Long-term Blood Pressure And Cardiac Protection

Objective To compare the effectiveness of transient prehypertensive treatment with losartan and amlodipine in spontaneously hypertensive rats (SHR) on long-term blood pressure and cardiac parametersMethod Four-week-old male SHRs were randomly treated with losartan (SHR-Los: 20mg/kg per day), amlodipine (SHR-Aml: 10mg/kg per day) or saline (SHR) by gavage for 6 weeks, age-and sex-matched Wistar Kyoto (WKY) rats were served as normal control. Rats were followed up until 46 weeks of age after drug cessation. Systolic blood pressure (SBP) was measured by tail-cuff method. Left ventricular mass index (LVMI) was calculated by left ventricle weight/body weight and myocardial collagen volume fraction (CVF) was evaluated using sirius red staining and image analysis. Left ventricular geometry and function were assessed by echocardiography. Plasma and myocardium angiotensin II (AngII) and aldosterone (Aldo) levels were measureded by radioimmunoassay. Cardiac AT1R and AT2R protein levels were determined by immunoblotting and brain natriuretic peptide (BNP) mRNA level was semiquantified by RT-PCR.Result During treatment (at weeks 10), SBP in SHR-Los and SHR-Aml were significantly reduced compared to untreated SHR but higher than that in WKY, no difference between SHR-Los and SHR-Aml was found. After drug withdrawal, SBP in SHR-Los was persistently reduced until age 46 weeks but restored to untreated SHR level in SHR-Aml from 30 weeks onwards. Compared to untreated SHR, the LVMI and CVF in SHR-Los were markedly decreased up to age 46 weeks, and the left ventricular ejection fraction (SHR-Los vs. SHR: 83.1±2.3% vs. 79.5±1.9%, P<0.05) and cardiac BNP mRNA level were improved. In contrast, comparable LVMI and elevated CVF were found in SHR-Aml, and the left ventricular EF fell significantly below untreated SHR at weeks 46 (SHR-Aml vs. SHR: 74.4±4.3% vs. 79.5±1.9%, P<0.05), with cardiac BNP mRNA level increasing significantly albeit slightly. Compared to untreated SHR, plasma and myocardium AngII and Aldo levels in SHR-Los were remarkably decreased, and cardiac AT1R protein level was down-regulated and AT2R up-regulated, whereas no significant difference of these indices was found between SHR-Aml and untreated SHR.Conclusion Prehypertensive treatment with losartan was more effective than amlodipine on delaying long-term blood pressure rise and meliorating cardiac structure and function, which might be achieved by inhibition of circulating and local renin-angiotensin systems...